We intend to define the participation of glucose, glucose metabolites and adenine nucleotides in the regulation of vascular tone and adrenergic nervous activity in heart and various vascular beds. In the isolated perfused heart, renal, mesenteric, splenic and pancreatic vasculature of rat, rabbit and cat, we will examine the effects of glucose and glucose deprivation, glucose metabolites and adenine and nucleotides on the vascular tone and vascular responsiveness to norepinephrine and sympathetic nerve stimulation. Modification of the vascular reactivity to nerve stimulation as affected by various agents will be related to the output of the norepinephrine. To define changes in the latter we will examine the synthesis, storage and inactivation of norepinephrine. The relationship of locally generated glucose metabolites to adrenergic neuroeffector events will be investigated after the inhibition of glucose metabolism. These studies should provide valuable information about some vascular diseases and neurogenic disorders such as diabetic neuropathy.